Joint OB / Pediatrics M&M conference PERINATAL CASE PRESENTATION AND DISCUSSION OF SEROLOGYCALLY POSITIVE MOTHER and INFANT FOR SYPHILIS Christian Castillo, MD BK Rajegowda, MD

Congenital Syphilis Syphilis is a Sexually transmitted disease Congenital Syphilis is a consequence of untreated or Inadequately treated maternal syphilis Rare but still occurs. A recent increase in cases is reported Prevention, early diagnosis and treatment will prevent fetal and neonatal infections

Presentation of cases Mother’s profiles Case #1 MR# Case #2 MR# Case #3 MR# Age Race HispanicBlack African American Caucasian Parity G3P0020G6P3024 G3P0020 PNC Neighborhood Health Center ??? First time in LH LH X 5 Late registrant at 34wk LH X 10 late registrant at 19 wk Time / Date serology RPR by Hx reactive and treated 2yrs ago at the health department. No documentation RPR 3/27/09 1:4 2/23/09 RPR 1:32 first visit 12/17/08 RPR 1:8 1 st visit Treatment 3/28/09 Penicillin B 2.4 IM 4/13/09 PNC #2 after Delivery at the clinic 3/6/09 Pen G 2.4 mill second V 3/20/09 pen G 2.4 mill 1/26/09 Documented only prescription given for Pen B X 3 Follow up serology tx 4/1/09Patient DC AMANo follow up titers before delivery 3/9/09 RPR 1:8 No Tx 3/23/09 RPR 1:8 no Tx Visit 4/7/09 refers to past Tx but not documentation Day of Delivery 3/28/094/4/09 4/19/09 Follow up Serology after Birth No follow up serology. Post Natal visit 4/13/09 4/6/09 after delivery RPR 1:4 4/6/09 Pen G 2.4 mill 4/19/09 RPR 1:16 Mother tx after delivery

Patient’s profile Case #1 Maternal tx undocumented, unknown PNC Delivery 3/28/09 FTAGA female born via C section at 40.3w by LMP Apgar 1 min and 5 min BWt: 3495 gms; L: 50.5 cms; HC: 34.5 cms; CC: 35 cms; Ag: 33 cms; SROM at 18:30hrs the day PTD, 13hr PTD; AF: clear Time of birth: 07:23hrs Normal VS and PE In view of unknown Labs and treatment prior to delivery, normal PE we decided to work up and treat this baby as unlikely syphilis Cord RPR 3/28/09 1:2 TPPA reactive CBC: 30.9/19.3/59/212 N73 Band 3 L 15 Long bone X ray, WNL CSF studies RBC WBC 5 Seg 70 Lymp 25 Mono 3 Eos 2 Glucose 46 protein 141 VDRL CSF no reactive 4/1/09 Tx Pen Benz Units IM 4/1/09 Discharge patient 5/7/09 Serum Patient’s RPR no reactive TPPA reactive IgG ab reactive

Patient’s profile Case # 2 Maternal Late registrant, PNC X 5 LH RPR 1:32 no follow up titers Delivery 4/4/09 FT AGA, NSVD at 38.1 by LMP to 24 y/o G6P3024 APGAR 1 min and 5 min B Wt: 3535 g, Length: 52.5 cm, HC: 35 cm, CC: 34 cm, AC: 35.5 cm ROM: 6. AF: clear at the time of birth 10.07am normal VS and PE 4/4/09 Cord RPR 1:16 TPPA reactive 4/5/09 Patient Plasma RPR 1:16 TPPA reactive 4/6/09 CSF studies RBC 475 WBC 4 Glucose 38 protein 132 VDRL CSF no reactive 4/7/09 Long bones X- R WNL 4/7/09, 4/8/09 / 4/9/09 Tx Pen Procaine until VDRL CSF no reactive 4/9/09 RPR 1:8 TPPA reactive 4/10/09 Pen G benz 4/10/09 Discharge

Patient’s profile Case # 3 Maternal Late registrant, PNC X 10 LH incomplete Treatment Delivery 4/19/09 FTAGA, NSVD at 39.6 weeks by LMP to 19 y/o Caucasian, G3P0020 APGAR: 1 min and 5 min B Wt: 3085 g, Length: 49 cm, HC: 34. cm, CC: 31 cm, AC: 33.5 cm ROM: 12 hrs ptd. AF: clear Normal PE 4/19/09 Cord RPR 1:4 TPPA reactive 4/19/09 and 4/21/09 Patient Plasma RPR 1:4 TPPA reactive 4/21/09 CSF RPR: NR Cell count RBC 1 WBC 4 clear. Glucose 44 protein 84 4/21/09 4/22/09 4/23/09 Pen Procaine 50,000 Units/Kg 4/21/09 Long bones X ray. WNL 4/24/09 Pen G benz 50, 000 units / Kg 4/24/09 Discharge 5/6/09 RPR: no Reactive IgG reactive

Congenital Syphilis The incidence of congenital syphilis corresponds to the incidence of disease in women. In almost three –quarter of cases the mother was not treated, or was inadequately treated. Incidence increased dramatically during late 1980 and early 1990 but subsequently decreases.

Congenital Syphilis Congenital Syphilis — United States After 14 years of decline in the United States, the rate of congenital syphilis increased 15.4% between 2006 and 2007 (from 9.1 to 10.5 cases per 100,000 live births). In 2007, 430 cases were reported, an increase from 373 in This increase in the rate of congenital syphilis may relate to the increase in the rate of P&S syphilis among women that has occurred in recent years. Congenital Syphilis by State In 2007, 29 states had rates of congenital syphilis that exceeded the 2010 target of one case per 100,000 live births. NYS reported 6.4 / in 2007

State/Area* Cases Georgia Hawaii20000 Idaho43000 Illinois Louisiana Maine00000 Maryland Massachusetts00000 Michigan Nevada New Jersey New Mexico63676 NEW YORK North Carolina Oklahoma12123 Oregon00002 Pennsylvania20148 Texas Washington00002 West Virginia00001 Wisconsin01201 Wyoming00000 U.S. TOTAL CDC Congenital Syphilis Reported cases and rates in infants < 1 year

Congenital syphilis lack a primary stage: because it is disseminated through blood Fetal infections can occur at any time during pregnancy Hepatomegaly is present in almost 100% Necrotizing funisitis within the matrix of the umbilical cord is consider highly indicative 60% of patients are asymptomatic Congenital Syphilis Clinical Presentation

Maternal Syphilis Dx and treatment Test During Pregnancy : All women should be screened for syphilis with a non Treponemal test – RPR / VRDL – early in pregnancy and preferably again at delivery. In high risk areas testing at the beginning of 3rd Trimester is also recommended. All Positive tests should be confirmed with a Treponemal test FTS-ABS /TPPA. For women treated during pregnancy FU serology testing is necessary to assess efficacy of therapy. Treatment with penicillin is the gold standard.

Maternal Syphilis Dx and treatment A single dose of Benzathine Penicillin therapy for early disease is only appropriate when is possible to document that there was a non reactive Syphilis test within the last Year. Some Give a second dose of Benzathine Penicillin 1 week after the first to improve the likelihood of a serology response in early disease. In all other cases the disease should be consider Latent syphilis of unknown duration for which 3 doses of Benzathine penicillin at weekly intervals are recommended. Follow up titers at 1,3,6,12 and 24 months decreases fourfold by 6 months and becomes negative by months. Failure to decrease titers is likely to be failure to treat or reinfection.

Evaluation of Newborn with Congenital Syphilis Mother’s serological status for syphilis Blood cord testing is inadequate for screening (could be non-reactive even when the mother is +) Infants born from seropositive mothers require a careful examination and a quantitative non-treponemal test (same test should be performed to the mother) If maternal titers have increased to > 4 folds and/or infant’s titer is 4 fold greater than the mother’s titers complete workup is warrant.

Evaluation of Newborn with Congenital Syphilis Untreated, inadequately treated, or treatment not documented Treated with a non-penicillin regimen (i.e.,erythromycin) Appropriately treated with PNC, but without the expected decrease in treponemal titers Syphilis treated < 1 month prior to delivery Syphilis treated before pregnancy but with insufficient serologic f/u to assess response

Evaluation of Newborn with Congenital Syphilis -work up- Physical Examination Quantitative non-treponemal serologic test of serum from the infant for syphilis (not from cord blood) VDRL and cell count from CSF Long bone X-rays (unless Dx established otherwise) Complete blood cell and platelet count Other tests include: Chest X-ray LFT Pathological examination of placenta or umbilical cord using specific fluorescent antitreponemal antibody staining Vision and hearing test

Evaluation of Newborn with Congenital Syphilis Transplacental transmission of nontreponemal and treponemal antibodies to the fetus can occur in a mother who has been treated appropriately for syphilis during pregnancy, resulting in + uninfected newborns, usually reverting by 4 to 6 months of age, whereas + FTA-ABS or TP-PA test result from passively acquired Ab and it may not become negative for 1 year or longer.

Congenital Syphilis Hepatomegaly Rash Ostitis, Metaphysitis, Periostitis Wimberger sign Nasal discharge Hydrops fetalis Petechial rash Necrotizing funisitis within the matrix of the umbilical cord

A more specific finding is localized bony destruction of the medial portion of the proximal tibial metaphysis (Wimberger’s sign). Other findings include metaphyseal serration (“sawtooth metaphyses”), and diaphyseal involvement with periosteal reaction. Decreased mineralization of the metaphyses of long bones of the upper extremities bilateral lytic lesions of the talus, calcaneous, and proximal tibia (Wimberger sign) medially Radiografic Abnormalities

Dermatology finding Congenital Syphilis Dermatological findings are quite variable, although palmar/plantar, perioral, and anogenital regions are classically described as being involved. The images to the left demonstrate findings at birth in an affected infant, with a desquamating eruption that was widespread over the entire body. These lesions are extremely infectious. Because of the variable lesions and clinical symptoms seen with CS, it has frequently been termed "the great imitator", and it is important to consider alternative diagnoses or vesiculobullous diseases that involve the palms and soles.

CDC guideline 2006 Congenital Syphilis Scenario 1. Infants with proven or highly probable disease and -an abnormal physical examination that is consistent with congenital syphilis, -a serum quantitative nontreponemal serologic titer that is fourfold higher than the mother’s titer, § or § -a positive dark field or fluorescent antibody test of body fluid(s). Recommended Evaluation CSF analysis for VDRL, cell count, and protein ¶ CBC and PLT ¶ Other tests as clinically indicated (e.g., long-bone radiographs, chest radiograph, liver-function tests, cranial ultrasound, ophthalmologic examination, and auditory brainstem response) Recommended Regimens Aqueous crystalline penicillin G 100,000–150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days

CDC guideline 2006 Congenital Syphilis Scenario 2. Infants who have a normal physical examination and a serum quantitive nontreponemal serologic titer the same or less than fourfold the maternal titer and the - mother was not treated, inadequately treated, or has no documentation of having received treatment; -mother was treated with erythromycin or other nonpenicillin regimen;** or** -mother received treatment <4 weeks before delivery. Recommended Evaluation CSF analysis for VDRL, cell count, and protein -CBC and PLT - Long –bone RX Recommended Regimens Aqueous crystalline penicillin G 100,000–150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days OR Benzathine penicillin G 50,000 units/kg/dose IM in a single dose Some specialists prefer the 10 days of parenteral therapy if the mother has untreated early syphilis at delivery

CDC guideline 2006 Congenital Syphilis Scenario 3. Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery; and mother has no evidence of reinfection or relapse. Recommended Evaluation No evaluation is required. Recommended Regimen Benzathine penicillin G 50,000 units/kg/dose IM in a single dose

CDC guideline 2006 Congenital Syphilis Scenario 4. Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the -Mother’s treatment was adequate before pregnancy, and -mother’s nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4). Recommended Evaluation No evaluation is required. Recommended Regimen No treatment is required; however, some specialists would treat with benzathine penicillin G 50,000 units/kg as a single IM injection, particularly if follow-up is uncertain.

Congenital Syphilis Conclusions The incidence of congenital syphilis corresponds to the incidence of disease in women. All pregnant women should be tested 1 st trimester and in the beginning of 3rd Trimester and at delivery. All positive test should be confirmed with a Treponemal Test, treat and follow up titers as per protocol. Documentation is an important aspect in the evaluation of treatment.

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